IUBMB Enzyme Nomenclature


Accepted name: procollagen-proline 4-dioxygenase

Reaction: procollagen L-proline + 2-oxoglutarate + O2 = procollagen trans-4-hydroxy-L-proline + succinate + CO2

For diagram of reaction, click here

Other name(s): P4HA (gene name); P4HB (gene name); protocollagen hydroxylase; proline hydroxylase; proline,2-oxoglutarate 4-dioxygenase; collagen proline hydroxylase; hydroxylase, collagen proline; peptidyl proline hydroxylase; proline protocollagen hydroxylase; proline, 2-oxoglutarate dioxygenase; prolyl hydroxylase; prolylprotocollagen dioxygenase; prolylprotocollagen hydroxylase; protocollagen proline 4-hydroxylase; protocollagen proline dioxygenase; protocollagen proline hydroxylase; protocollagen prolyl hydroxylase; prolyl 4-hydroxylase; prolyl-glycyl-peptide, 2-oxoglutarate:oxygen oxidoreductase, 4-hydroxylating; procollagen-proline 4-dioxygenase (ambiguous)

Systematic name: procollagen-L-proline,2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)

Comments: Requires Fe2+ and ascorbate.The enzyme, which is located within the lumen of the endoplasmic reticulum, catalyses the 4-hydroxylation of prolines in -X-Pro-Gly- sequences. The 4-hydroxyproline residues are essential for the formation of the collagen triple helix. The enzyme forms a complex with protein disulfide isomerase and acts not only on procollagen but also on more than 15 other proteins that have collagen-like domains.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9028-06-2


1. Hutton, J.J., Jr., Tappel, A.L. and Udenfriend, S. Cofactor and substrate requirements of collagen proline hydroxylase. Arch. Biochem. Biophys. 118 (1967) 231-240.

2. Kivirikko, K.I. and Prockop, D.J. Purification and partial characterization of the enzyme for the hydroxylation of proline in protocollogen. Arch. Biochem. Biophys. 118 (1967) 611-618.

3. Kivirikko, K.I., Kishida, Y., Sakakibara, S. and Prockop, J. Hydroxylation of (X-Pro-Gly)n by protocollagen proline hydroxylase. Effect of chain length, helical conformation and amino acid sequence in the substrate. Biochim. Biophys. Acta 271 (1972) 347-356. [PMID: 5046811]

4. Berg, R.A. and Prockop, D.J. Affinity column purification of protocollagen proline hydroxylase from chick embryos and further characterization of the enzyme. J. Biol. Chem. 248 (1973) 1175-1182. [PMID: 4346946]

5. John, D.C. and Bulleid, N.J. Prolyl 4-hydroxylase: defective assembly of α-subunit mutants indicates that assembled α-subunits are intramolecularly disulfide bonded. Biochemistry 33 (1994) 14018-14025. [PMID: 7947811]

6. Lamberg, A., Pihlajaniemi, T. and Kivirikko, K.I. Site-directed mutagenesis of the α subunit of human prolyl 4-hydroxylase. Identification of three histidine residues critical for catalytic activity. J. Biol. Chem. 270 (1995) 9926-9931. [PMID: 7730375]

7. Myllyharju, J. and Kivirikko, K.I. Characterization of the iron- and 2-oxoglutarate-binding sites of human prolyl 4-hydroxylase. EMBO J. 16 (1997) 1173-1180. [PMID: 9135134]

8. Kivirikko, K.I. and Myllyharju, J. Prolyl 4-hydroxylases and their protein disulfide isomerase subunit. Matrix Biol 16 (1998) 357-368. [PMID: 9524356]

[EC created 1972, modified 1981, modified 1983, modified 2017]

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